Recurrent Pregnancy Loss (RPL) is a specific medical condition affecting between 1% and 5% of couples attempting to conceive. While a single pregnancy loss is common, RPL is a complex health issue that warrants a comprehensive medical investigation. Understanding RPL is the first step toward finding potential causes and exploring management strategies for a future healthy pregnancy. A detailed evaluation can help identify underlying factors, though many cases remain without a clear explanation.
Defining Recurrent Pregnancy Loss
Recurrent Pregnancy Loss is defined as the experience of two or more failed clinical pregnancies before 20 weeks of gestation. Most medical societies recommend investigation after two losses. A clinical pregnancy is one confirmed by ultrasound or histopathological examination, differentiating it from an early biochemical loss. The majority of losses occur in the first trimester.
RPL is classified into two types based on prior obstetric history. Primary RPL refers to losses experienced by a woman who has never had a live birth beyond 24 weeks. Secondary RPL is diagnosed in women who have had at least one successful live birth followed by subsequent losses. While the prognosis for a future live birth is high for both groups, women with primary RPL may have a higher risk of subsequent obstetric complications, such as preterm delivery.
Investigating Underlying Causes
A thorough investigation into RPL focuses on several major categories of medical factors. Genetic factors are a common cause, with approximately 50% of all early pregnancy losses related to random chromosomal abnormalities (aneuploidy) in the developing embryo. A smaller percentage (2% to 5% of couples) carry a balanced structural chromosomal rearrangement, such as a reciprocal or Robertsonian translocation. This balanced rearrangement can lead to an unbalanced chromosome complement in the embryo, resulting in pregnancy loss.
Anatomical factors involving the uterus account for approximately 10% to 15% of cases by impairing implantation and growth. Congenital abnormalities, such as a septate uterus (where tissue divides the uterine cavity), are the most common uterine malformation linked to RPL. Acquired structural issues, including large submucosal fibroids, intrauterine scar tissue (Asherman syndrome), or uterine polyps, can also interfere with pregnancy maintenance.
Endocrine and metabolic disorders contribute to 17% to 20% of RPL cases. Uncontrolled systemic conditions like diabetes mellitus and thyroid dysfunction, specifically overt hypothyroidism, are known risk factors. Polycystic Ovary Syndrome (PCOS) is also implicated in some cases, likely due to resulting hormonal imbalances.
Immunological factors, particularly Antiphospholipid Syndrome (APS), are a significant treatable cause, accounting for 8% to 42% of RPL cases. APS is an autoimmune disorder characterized by specific antibodies that promote blood clotting, potentially leading to microthrombosis in the placental blood vessels. These antibodies—lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein I—can impair necessary blood flow between the mother and the developing fetus.
Diagnostic Testing Protocols
Blood and Genetic Testing
Evaluation typically begins with blood tests to check for endocrine and immunological issues. These include screening for thyroid dysfunction (TSH), diabetes (hemoglobin A1c), and sometimes prolactin levels. Testing for Antiphospholipid Syndrome involves specific blood work to detect the three key autoantibodies. If a positive result is found, the test is repeated at least twelve weeks later to confirm the persistent presence of the antibodies necessary for an APS diagnosis.
Genetic testing is routinely performed on both parents through peripheral karyotyping to screen for balanced structural chromosomal abnormalities. If a pregnancy loss occurs, a 24-chromosome microarray analysis of the tissue (products of conception) may be performed to identify aneuploidy in the embryo.
Uterine Imaging
Imaging studies are necessary to assess the uterine structure for anatomical issues. A pelvic ultrasound, often a 3D transvaginal scan, is a non-invasive way to examine the shape of the uterus and look for acquired lesions like fibroids. More detailed assessments may involve:
- Hysterosalpingogram (HSG), which uses dye and X-ray to visualize the uterine cavity and fallopian tubes.
- Sonohysterography, which uses saline infusion to enhance ultrasound visualization.
- Hysteroscopy, which uses a small camera inserted through the cervix to directly assess the inside of the uterus.
Management and Treatment Strategies
Treatment for RPL is highly individualized and depends entirely on the specific cause identified. When a structural uterine abnormality like a septate uterus is found, surgical correction via hysteroscopy is often recommended, as it can significantly improve the subsequent live birth rate. Acquired issues like submucosal fibroids or intrauterine scar tissue may also be surgically removed.
For women diagnosed with Antiphospholipid Syndrome, the standard medical approach involves a combination of low-dose aspirin and a blood thinner (heparin) administered throughout the pregnancy to prevent blood clot formation in the placental circulation. Managing endocrine disorders involves treating the underlying condition, such as optimizing blood sugar control or correcting thyroid hormone levels with medication.
Couples carrying a balanced chromosomal translocation are often referred for genetic counseling. They may pursue in vitro fertilization (IVF) with preimplantation genetic testing for structural rearrangements (PGT-SR) to select embryos with the correct chromosome complement. For the approximately 50% of couples whose RPL remains unexplained, supportive care is the primary intervention, including close monitoring and psychological support. Even without a specific diagnosis, the prognosis for a successful pregnancy is encouraging, with many couples having a 60% to 80% chance of a live birth.